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    The Tec kinase ITK is required for homeostasis and anti-viral immune protection in the intestine

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    Authors
    Cho, Hyoung-Soo
    Faculty Advisor
    Leslie J. Berg
    Academic Program
    Immunology and Microbiology
    UMass Chan Affiliations
    Pathology
    Document Type
    Doctoral Dissertation
    Publication Date
    2018-10-10
    Keywords
    T cells
    Mucosal Immunology
    CD4 T helper cells
    T helper cell differentiation
    PRN694
    CD8 T cells
    Intestine
    Innate Lymphoid Cells
    ILC2
    Tissue Homeostasis
    Immunity
    Immunology of Infectious Disease
    Immunopathology
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    Abstract
    The Tec kinase ITK is activated by TCR stimulation and also required for TCR downstream signaling. Previous studies have reported differential roles of ITK and another Tec family kinase RLK in CD4+ TH differentiation and effector function. However, these findings are confounded by the complex T cell developmental defects in Itk-/- mice. Furthermore, the function of ITK in tissue-resident T cells in the intestine and anti-viral immune response to a persistent infection has not been studied previously. In addition to T cells, recent studies have indicated an expression of ITK in ILC2, but not in other ILC subsets. Yet, the role of ITK in ILC2 has not been characterized. Here, I have examined the role of ITK and RLK in CD4+ TH subsets using a small molecule inhibitor PRN694. I found that PRN694 impaired TH1 differentiation in vitro, and PRN694 administration prevented TH1-mediated colitis progression in vivo. In an MHV68 infection model, Itk-/- mice failed to control viral replication in the intestine, while gut-homing of CD8+ T cells was greatly impaired. Finally, I found that ILC2 number was markedly reduced in the intestine of Itk-/- mice. Gut-specific defect of Itk-/- ILC2 is associated with a low availability of IL-2 in the intestine of Itk-/- mice. Collectively, these data suggest that ITK is important in T cell migration to the intestine and ILC2 homeostasis in the intestine, thereby contributing to the protective response to a latent virus and intestinal tissue homeostasis.
    DOI
    10.13028/7r7q-7829
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/32387
    Rights
    Copyright is held by the author, with all rights reserved.
    ae974a485f413a2113503eed53cd6c53
    10.13028/7r7q-7829
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    Morningside Graduate School of Biomedical Sciences Dissertations and Theses

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